In a special breeding project with the goal of developing one or more models of autoimmune disease, rabbits are being bred within our colony for susceptibility to disease induction. The initial focus of our study is a rabbit model of human Systemic Lupus Erythematosus (SLE). It is known that in man some genes affect susceptibility to several different autoimmune diseases. Thus selective breeding may result broader susceptibility to autoimmune diseases. SLE is a complex, chronic autoimmune disorder that predominately affects young women. Clinical symptoms may include rash, arthritis, nephritis, and neurological disruption (including cognitive decline, seizures, psychosis). SLE is characterized by the production of autoantibodies to various nuclear antigens and double-stranded DNA (dsDNA). Initial protocols are based on published reports that immunization of rabbits with a peptide sequence shared by Epstein-Barr Virus and the spliceosomal autoantigen Sm B/B' elicited anti-Sm and anti-dsDNA autoantibodies in some rabbits. This first report was not confirmed by a second group. However, it is well established that the etiology of lupus in man has a strong genetic component. We hypothesize that genetic diversity among the rabbits used in two independent published studies contributed to the failure of the second group to reproduce the initial observation. We are repeating the published immunization experiments now using our genetically defined rabbit colony in an attempt to induce a lupus-like syndrome and to develop a lineage of susceptible animals. In addition to the Sm peptide we are also immunizing rabbits with a MAP 8 conjugate of an NMDA glutamate receptor-derived peptide (GR). It was recently reported that a mouse anti dsDNA antibody, as well as some anti-dsDNA from human SLE patients, could cross-react and bind glutamate receptors. Receptor occupancy and/or neuronal death caused by such antibodies may explain some of the CNS symptoms in lupus patients. In experiments in progress we find that immunization with both MAP 8-conjugated peptides elicits anti-peptide responses. In addition, comparisons of preimmune and post-immunization sera suggest that levels of anti-dsDNA and antinuclear antibodies have increased in some MAP-peptide immunized rabbits. Noteably, if rabbits immunized with MAP-8-GR produce antibodies to dsDNA, this would confirm and extend previous observations in mice. These preliminary results, if confirmed in ongoing studies, may further our understanding of the development of autoantibodies in SLE as well as of the effects of autoantibodies on the CNS in lupus. Finally, by breeding immunized rabbits and their progeny we hope to develop a genetically susceptible but non-inbred strain of rabbits.